Resection Arthroplasty of the Proximal Tibia

Custom made total arthroplasty of the knee with resection of the upper third of the tibia was performed in two cases. The follow-up results showed good function 1 year later. The procedure is recommended in benign as well as selected malignant tumors of the proximal tibia.     

Inhibition of ADAM10 in satellite cells accelerates muscle regeneration following muscle injury

Muscle injury is one of the most common orthopedic and sports disorders. For severe cases, surgical repair may be indicated; however, other than immobilization and the administration of anti‐inflammatory drugs there is currently no effective conservative treatment for this condition. Satellite cells (SCs) are muscle‐specific stem cells and are indispensable for muscle regeneration after muscle injury. SCs are activated upon muscle injury to proliferate and differentiate into myoblasts, which subsequently fuse into myofibers and regenerate the damaged muscle. We have previously shown that ADAM10, a membrane‐anchored proteolytic enzyme, is essential for the maintenance of SC quiescence by activating the Notch signaling pathway in SCs. Because suppression of ADAM10 activity in SCs can activate SC differentiation, we asked whether inactivation of ADAM10 in SCs after muscle injury could enhance muscle regeneration. Using Adam10 conditional knockout mice, in which ADAM10 activity can specifically be suppressed in SCs, we found that partial inactivation of ADAM10 accelerates muscle regeneration after muscle injury. Nearly identical results were obtained by the administration of GI254023X, a selective ADAM10 inhibitor. The findings of the present study thus indicate that transient enhancement of SC differentiation after muscle injury expedites muscle regeneration and that ADAM10 can be a potential molecular target in treating muscle injuries. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2259–2265, 2018.

     

Neuronal antibodies and paraneoplastic sensory neuropathy in thymoma

Thymoma, a common anterior mediastinal tumour, may present with paraneoplastic neurological symptoms. The presence of neuronal anti-Hu paraneoplastic antibodies in thymoma patients is very rare. Here, we describe a patient who presented with symptoms of a sensory peripheral neuropathy in the presence of onconeural antibodies cross-reactive with Hu antigen, in whom an underlying thymoma was diagnosed. Subsequent minimally invasive thymomectomy improved her neurological symptoms significantly.     

Alendronate prevents femoral periprosthetic bone loss following total hip arthroplasty: prospective randomized double-blind study.

Following total hip arthroplasty (THA), femoral periprosthetic bone undergoes a remodeling process that results in bone loss in its proximal regions that may compromise the long-term outcome of THA. Periprosthetic bone loss mainly occurs during the first postoperative months. The question is whether a postoperative treatment with alendronate is effective in reducing periprosthetic bone loss and which doses and duration of treatment are required. In a 12-month prospective, randomized double-blind study, 51 patients undergoing cementless THA were treated postoperatively either with a daily dose of 20 mg alendronate for 2 months and 10 mg for 2 months thereafter (group I), with 20 mg of alendronate for 2 months and 10 mg for 4 months thereafter (group II), or treated with placebo (group III). Proximal femoral bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry (DEXA) and serum biochemical markers of bone turnover bone specific alkaline phosphatase, osteocalcin, and C-terminal telopeptides (CTX-I) were assayed. Six months of alendronate treatment significantly reduced (p<0.001) bone loss in proximal medial region (-10%) compared with placebo (-26%). All biochemical markers of bone turnover were suppressed by alendronate. These data suggest that alendronate administered for the first 6 postoperative months following THA was effective in preventing early periprosthetic bone loss.     

Changes of femoral periprosthetic bone mineral density 6 years after treatment with alendronate following total hip arthroplasty

Earlier osteodensitometric results of femoral periprosthetic bone showed that postoperative antiresorptive treatment with alendronate following total hip arthroplasty (THA) reduces the periprosthetic bone loss that commonly occurs in the first months after surgery. However, whether alendronate can prevent periprosthetic bone loss over the long term, or if bone loss occurs after discontinuing alendronate is unknown. Femoral periprosthetic bone mineral density (BMD) was assessed in 49 patients 6 years after cementless total hip arthroplasty using dual energy X‐ray absorptiometry. Twenty‐nine patients were treated postoperatively with alendronate and 20 control patients received no treatment. All patients were followed up at 12 months after surgery in a prospective randomized study. The bone mineral density was evaluated in 7 regions of interest according to the Gruen protocol. Six years after total hip arthroplasty, no significant changes were detected in femoral periprosthetic BMD when compared with results at 1 year, and the bone loss in patients with postoperative alendronate treatment was still significantly less than those without treatment. These results suggest that the prevention of femoral periprosthetic bone loss following THA achieved by postoperative antiresorptive treatment with alendronate is of long‐standing effect, and further bone loss does not occur after the first postoperative year. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:183–188, 2009     

Lack of topographical specificity in sensory nerve regeneration through muscle grafts in rats.

Regenerating sensory axons of each receptor class make new connections with similar denervated receptors. This study investigates to what extent these axons return to their original receptive field. The lateral cutaneous nerves of the thigh in rats were divided and allowed to regenerate across a 6 mm. gap interposed with frozen and thawed muscle graft towards their original distal nerve stump and a "foreign" sensory nerve, the saphenous nerve. 16 weeks later, myelinated axon counts of 26 pairs of distal nerves showed no preferential growth towards the original receptive field. Lack of topographic specificity during sensory nerve regeneration may explain the faulty localisation of sensation after nerve repair in clinical practice. Following sensory nerve regeneration, the somatosensory cortex receives accurate afferent information but from disparate skin sites; this probably alters the relationship of overlapping sensory fields and may be the cause of distorted pattern recognition.     

Cytokine expression in muscle following traumatic injury

Heterotopic ossification (HO) occurs at a high frequency in severe orthopaedic extremity injuries; however, the etiology of traumatic HO is virtually unknown. Osteogenic progenitor cells have previously been identified within traumatized muscle. Although the signaling mechanisms that lead to this dysregulated differentiation pathway have not been identified, it is assumed that inflammation and fibrosis, which contribute to an osteoinductive environment, are necessary for the development of HO. The hypothesis of this study was that cytokines related to chronic inflammation, fibrogenesis, and osteogenesis become up‐regulated following severe muscle trauma where HO forms. Classification of these cytokines by their differential expression relative to control muscle will provide guidance for further study of the mechanisms leading to HO. Real‐time RT‐PCR analysis revealed no significant up‐regulation of cytokines typically associated with HO (e.g., BMP‐4, as observed in the genetic form of HO, fibrodysplasia ossificans progressiva). Instead, the cytokine gene expression profile associated with the traumatized muscle included up‐regulation of cytokines associated with osteogenesis and fibrosis (i.e., BMP‐1 and TGF‐β₁). Using immunohistochemistry, these cytokines were localized to fibroproliferative lesions, which have previously been implicated in HO. This study identifies other cell and tissue‐level interactions in traumatized muscle that should be investigated further to better define the etiology of HO. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1613–1620, 2011.     

Sensory neurotization of muscle: past,present and future considerations

Research has shown that temporary innervation by a sensory neuron can provide trophic support to a denervated muscle and stave off muscular atrophy until motor neuron transfer is viable. This so called ‘sensory protection’ allows for improved outcomes when motor reinnervation able to occur. The theoretical benefit of sensory neurotization is hypothesized to maintain tissue architecture of the end organ due to tropic effects of stimulation. While the literature supports direct motor neurotization from 2 to 4 months post-injury, patient factors including the location of the injury and loss of nerve can preclude this therapeutic window. When direct neurotization is not possible, or there is a long distance to traverse for reinnervation, sensory neurotization may be beneficial. The theorized trophic stimulation enabling end organ architectural maintenance provided by sensory neurotization has been shown to allow for delayed direct motor neurotization without the irreversible sequelae of prolonged denervation. This is a review of the pathogenesis of nerve injury and a literature review of sensory neurotization. An analytical search of the literature in PubMed was performed in order to find articles pertinent to the topic of sensory neurotization, including experimental data from both animal models and case reports in humans.     

Comparison of reinnervation for preservation of denervated muscle volume with motor and sensory nerve: an experimental study

Prevention of the atrophy of denervated muscles is essential for a good outcome in facial contouring and oral reconstruction. In this study, we compared the effectiveness of end-to-end and end-to-side neurorrhaphy of the motor nerve, and end-to-end neurorrhaphy of the sensory nerve, all of which are frequently used in such reconstruction for the prevention of muscle atrophy. Wistar rats were divided into four groups: group 1, motor nerve division of semi-membranosus without repair; group 2, motor nerve division and end-to-end coaptation to the saphenous nerve; group 3, motor nerve division and end-to-side coaptation to the sciatic nerve; and group 4, motor nerve division and end-to-end repair. Measurement of semi-membranosus volume, histological evaluation and staining of neuromuscular junctions that were carried out 3 months postoperatively revealed that muscle volume preservation was larger in groups 3 and 4 than in the other two groups (p<0.05), but slightly superior in group 4 (p<0.05). There was no statistical difference between groups 2 and 1; histologically, muscle architecture was better preserved in group 2 than in group 1; reactivation of the neuromuscular junctions was observed in all except group 1. End-to-side repair of motor nerves is one of the better options for the preservation of muscle volume when end-to-end nerve repair is not indicated. Sensory protection may also provide some advantages in the preservation of muscle volume.     

Neuronal populations capable of regeneration following a combined treatment in rats with spinal cord transection

Axonal regeneration after spinal cord injury (SCI) in adult mammals is limited by inhibitors associated with myelin and the glial scar. To overcome these inhibitors, a combined approach will be required. We have previously demonstrated that, following complete SCI in rats, a combination of bridging the lesion with Schwann cell (SC)-filled guidance channels, olfactory ensheathing glia implantation, and chondroitinase ABC delivery promoted regeneration of serotonergic fibers into the lumbar spinal cord. In addition, this combined treatment significantly improved locomotor recovery. To complement these findings, we repeated this combined treatment to assess whether fibers other than serotonergic axons were able to regenerate into the caudal spinal cord. In this experiment, we injected the retrograde tracer FluoroGold (FG) into the spinal cord caudal to a complete transection in a control and a treated group. FG-positive cells rostral to the lesion and in the brainstem of animals in the treated group showed that axons were able to regenerate across the SC bridge and into the caudal spinal cord. Treated rats had labeled cells in the reticulospinal nuclei, vestibular nuclei, and the raphe nucleus as well as in the spinal cord. Cell numbers were highest in the thoracic spinal cord and the lateral vestibular nucleus. Determining the mechanisms for the superior capability of these cell populations to regenerate may provide valuable clues in the design of future treatment approaches.     

重组慢病毒介导心脏营养素-1基因转染延缓小鼠失神经骨骼肌萎缩

目的 探讨重组慢病毒介导的心脏营养素-1(cardiotrophin-1,CT-1)基因转染延缓小鼠失神经骨骼肌萎缩的疗效.方法 将36只Swiss小鼠,随机分为实验组和对照组,每组18只,切断胫神经,建立右下失神经支配肌萎缩模型.于实验组和对照组失神经腓肠肌分别转染重组慢病毒载体Lenti-GFP-CT-1和Lenti-GFP溶液20μl(108TU/ml),转染后2、4周,每个时间点分别取3只小鼠,于荧光显微镜下观察绿色荧光蛋白(GFP)的表达、Western blot检测CT-1的表达;取6只小鼠行单次收缩力、强直收缩力的检测,测定肌湿重、肌纤维横截面积,并观察肌纤维超微结构的变化.结果 慢病毒转染2,4周,两组腓肠肌中均可见大量GFP表达.Western blot检测显示实验组失神经腓肠肌中有明显的CT-1表达(P均<0.01).转染2周,实验组肌肉单次收缩力恢复率、强直收缩力恢复率、肌湿重维持率和肌纤维横截面积分别为[(47.61±6.25)%,x-±s,下同]、(56.08±5.47)%、(63.02±5.23)%、(1372.42±149.73)μm2,均明显高于对照组,后者分别为(27.23±5.06)%、(30.78±4.67)%、(52.41±4.98)%、(1147.28±128.67)μm2(P均<0.01);4周时,实验组上述各项指标分别为(33.13±4.76)%、(36.59±5.67)%、(51.46±5.36)%、(1209.12±142.57)μm2,仍明显高于对照组,后者分别为(16.40±5.48)%、(15.35±4.08)%、(39.15±6.12)%、(989.45±136.12)μm2(P均<0.01).此外,实验组肌浆网的扩张程度明显减轻.结论 慢病毒介导的基因治疗有较高的转染效率,其介导的CT-1基因转染能有效延缓小鼠失神经骨骼肌的萎缩,其疗效至少可以维持4周.     

Bone mineral density of the proximal tibia following uncemented arthroplasty

Bone mineral density (BMD, g/cm2) was measured using dual-photon absorptiometry (DPA) in selected areas of the proximal tibia following uncemented PCA knee prosthesis. In nine patients with 14 alloplastic operations, measurements were taken at 3-6-month intervals for the first 3 1/2 years after operation. There was a significant increase in BMD of about 15% during the first 6 months after operation. The following year it remained increased, although not significantly, compared with the initial values, then gradually diminished. Increased bone density after arthroplasty may be explained mainly by stimulation of bone formation from weight bearing due to improved walking ability. Stress shielding of the proximal part of the supporting tibial bone did not seem to occur.     

Effect of intermittent administration of adiponectin on bone regeneration following mandibular osteodistraction in rabbits

Adiponectin, a protein hormone produced and secreted exclusively by adipocytes, was reported to increase bone mass and stimulate angiogenesis. However, the effect of adiponectin on bone regeneration following distraction osteogenesis has not yet been reported. In this study, rapid unilateral mandibular osteodistraction (distraction rate = 2 mm/day) was applied in 24 New Zealand white rabbits. The animals were then randomly divided into groups A and B (n = 12 for each group). At the 1st, 3rd, and 5th day of the distraction, 200 µl PBS and 200 µl PBS contained 2 µg rh‐adiponectin was intermittently injected into the distraction gap in groups A and B, respectively. At 6 weeks after the end of distraction, the rabbits were sacrificed, and the distracted mandibles were harvested and processed for radiography, dual energy X‐ray absorptiometry (DXA), micro‐CT, histology, and three‐point bend testing. Under a rapid distraction, immature bone formation was seen in the distracted callus from group A. However, much greater bone formation and higher bone mineral density (BMD) and bone mineral content (BMC) of the distracted callus were observed in group B. Such finding was confirmed by histological, micro‐CT examinations, and mechanical strength test. The results of this study suggest that intermittent administration of adiponectin can promote bone regeneration following rapid mandibular osteodistraction in rabbits. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1081–1085, 2011     

Motor reinnervation of a denervated muscle by using a sensory nerve: an experimental study on gluteus maximus muscle of the rat

PURPOSE: This study aimed at developing a new muscle reinnervation technique using a sensory nerve. METHODS: We attempted innervation of the rat gluteus maximus muscle using the lateral femoral cutaneous nerve (LFCN). We placed the gluteus maximus muscle into the fibroadipose tissue in the distribution of the LFCN in 24 rats. In one group, the original innervation remained intact. In the second and third groups, the muscles were denervated, and in the third group, the proximal end of the nerve to the gluteus maximus was sutured to the distal end of the divided LFCN. We compared muscle reinnervations of the groups by using electrophysiologic evaluation of the muscle contractions, light microscope evaluation of the axonal regenerations, and scanning electron microscope evaluation of the actin-myosin structures of the muscles at the end of an elapsed waiting period. RESULTS: At the end of electrophysiologic evaluation, the mean area of compound muscle action potentials measured in group 1 was 3.8 ms/mV; in group 2, 0.0; and in group 3 (experimental group), 0.5. Axonal regeneration was observed distal to the coaptation, and actin-myosin structures were mostly spared in group 3. CONCLUSIONS: This study explored the feasibility of a new flap prefabrication method that aims at developing reinnervation of a denervated muscle by means of a sensory nerve. In light of histologic and electrophysiologic findings, this type of reinnervation is possible.